This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypercholesterolemia is a risk factor for atherosclerosis. Loss of endothelial nitric oxide (NO) which protects the vasculature through promoting vasodilation (VD) coupled with increased oxidative stress is associated with systemic vascular dysfunction. Possible mechanisms 1) increased vascular arginase activity and 2) endothelial nitric oxide synthase (eNOS) "uncoupling" contributing to oxidative stress. We pair in vivo (intradermal microdialysis) and in vitro experiments (skin biopsy) examining mechanisms in hypercholesterolemics (HC) and comparing with age-matched non-hypercholesterolemics (NC). We investigate reducing cholesterol with a hydroxymethylglutaryl (HMG) CoA reductase inhibitor.